Design, Synthesis, Biological Evaluation, DFT Calculations, and Molecular Docking Investigations of ^99m Tc‐Rosuvastatin as a Promising Radiopharmaceutical for Liver Targeting

Rosuvastatin is a lipid‐lowering medication belonging to the statin group that acts as a selective inhibitor of 3‐hydroxy‐3‐methyl‐glutaryl coenzyme A (HMG‐CoA) reductase, a rate‐limiting step of cholesterol biosynthesis in the liver. 99m Tc‐rosuvastatin was synthesized aiming to develop a potential radiopharmaceutical for targeting liver. The in vitro stability and radiochemical yield were investigated, and the yield of the 99m Tc‐rosuvastatin complex was 89.5 ± 1.85%. Biodistribution study revealed a good preferential localization of 99m Tc‐rosuvastatin in liver tissues suggesting using the labeled compound as a promising liver imaging candidate. The favorable sites of Tc labeling were determined by the analysis of natural atomic charges using the DFT method at the B3LYP/LanL2DZ level of theory. Binding modes between the rosuvastatin (and its stable technetium complex) and the human HMG‐CoA reductase were determined using molecular docking, and the obtained results revealed the effectiveness of technetium in increasing the binding affinity to the active residues of HMG‐CoA reductase.